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Celiac.com 07/13/2017 - Until recently, duodenal biopsy was considered the gold standard for diagnosing celiac disease, but that is changing.
A number of studies have shown that celiac disease can be diagnosed using serological tests alone, but many clinicians have yet to embrace this approach.
In both retrospective and prospective studies, one research team showed that certain IgA-tissue transglutaminase antibodies levels can predict celiac disease in adults 100% of the time.
After making some adjustments to the analytical method for measuring the antibody, a team of researchers recently set out to to determine whether such serum tests can reliably diagnose celiac disease in large numbers adult patients without the need for small bowel biopsy.
The research team included GKT Holmes, JM Forsyth, S Knowles, H Seddon, PG Hill, and AS Austin.
They are variously associated with the Royal Derby Hospital, the Department of Pathology, and the Derby Digestive Diseases Centre at the Royal Derby Hospital in Derby, UK.
For their study, the team conducted a retrospective analysis in an unselected series of 270 adult patients who underwent small bowel biopsies and the measurement of serum IgA-tissue transglutaminase antibody levels from 2009 to 2014.
At an IgA-tissue transglutaminase antibody cut-off greater than 45 U/ml (>8×upper limit of normal+2SDs) the positive predictive value for celiac disease in this cohort was 100%; 40% of cases were above this cut-off.
The team found that they could use IgA-tissue transglutaminase antibody levels to reliably diagnose celiac disease in a high proportion of these adult patients.
This study adds to the growing body of evidence that supports the diagnosis of celiac disease without a mandatory small bowel biopsy.
As a realist of these findings, the study team has changed the diagnostic guidelines for their center, and will now make celiac diagnosis based on cut-off levels of IgA-tissue transglutaminase.
This is exciting news. For many, many years, the biopsy was considered the gold standard for diagnosing celiac disease.
By eliminating biopsies in favor of IgA-tissue transglutaminase levels, diagnosing celiac disease could become much easier and even cheaper.
Do you have celiac disease? Did you receive a biopsy for diagnosis? How do you feel about celiac diagnosis without biopsy? Share your thoughts below.
Source:
Eur J Gastroenterol Hepatol. 2017 Jun;29(6):640-645. doi: 10.1097/MEG.0000000000000841.

Celiac.com 12/12/2016 - Studies suggest that celiac disease affects about 0.5% to 1% of the North American population. There is no good screening data based on small intestinal biopsy performed during routine endoscopic evaluation.
Researcher Hugh James Freeman, MD CM FRCPC FACP, of the Gastroenterology unit in the Department of Medicine at the University of British Columbia in Vancouver, British Columbia, recently set out to review the detection of adult celiac disease using duodenal screening biopsies over a 30-year period.
Dr. Freeman reviewed data from patients referred between January 1982 and December 2011 for evaluation of gastrointestinal symptoms, requiring elective investigative upper endoscopic evaluation, and who underwent duodenal biopsies to determine whether changes of adult celiac disease were present. He found a total of 9,665 patients, including 4,008 male and 5,657 female, who underwent elective endoscopy and duodenal biopsy.
Of these, 234, about 2.5%, showed celiac-associated physical changes, including 73 males (1.8%) and 161 females (2.8%). During the first 20 years, the number of biopsy-positive patients in five-year intervals progressively decreased, while over the next 10 years, the number progressively increased.
Dr Freeman's results indicate that celiac disease is far more common in specialist practice than has been suggested by data from healthy populations using serological screening.
Because endoscopic duodenal biopsy is so effective in spotting celiac-related damage, Dr. Freeman suggests it be routinely considered in all patients receiving elective endoscopic evaluation.
Source:
Can J Gastroenterol. 2013 Jul; 27(7): 405–408. PMCID: PMC3956015

Celiac.com 08/19/2013 - Data from blood studies suggest that about 1% or so of North Americans have celiac disease. However, there is no good screening data based on small intestinal biopsy performed during routine endoscopic evaluations.
Researcher H.J Freeman recently set out to determine rates of detection of adult celiac disease via duodenal screening biopsies over a thirty year period.
For his study, he looked at patients referred between January 1982 and December 2011 for evaluation of gastrointestinal symptoms that required elective investigative upper endoscopic assessment, and who underwent duodenal biopsies to determine whether changes of adult celiac disease were present.
Freeman looked at a total of 9665 patients, including 4008 (41.5%) males and 5657 (68.5%) females, who underwent elective endoscopies and duodenal biopsies.
Overall, 234 patients (2.4%) exhibited changes of celiac disease. That included 73 males (1.8%) and 161 females (2.8%).
During the first 20 years, the number of biopsy-positive patients in five-year intervals progressively decreased, while, during the next 10 years, the number progressively increased.
From this study, the team concludes that celiac disease is far more common in specialist practice than has been suggested in the evaluation of healthy populations using serological screening studies.
Endoscopic duodenal biopsy is an important way to spot underlying celiac disease and should be routinely considered in all patients undergoing an elective endoscopic evaluation.
They also note that the appearance of biopsy-defined celiac disease may be influenced by non-inherited factors, possibly environmental, which alter its detection over time.
Source:
Can J Gastroenterol. 2013 Jul;27(7):405-8.

Celiac.com 06/23/2009 - Fibroblasts are one of the most important components in inflammation and tissue remodeling process, and are thought to be involved in the pathogenesis of autoimmune disorders such as celiac disease.
Attempts to better understand the role played by fibroblasts in celiac diseases have been hampered by the absence of specific models.
A team of researchers recently set out to isolate and culture primary fibroblasts from endoscopic duodenal biopsies of celiac and non-celiac subjects, and to analyze their growth patterns and any morphometric characteristics.
The research team obtained 60 tissue samples via duodenal biopsy from 20 celiac patients and 114 samples from 38 non-celiac subjects. The team then mechanically chopped and enzymatically digested in order to obtain primary cell cultures.
Using cultured cells, the researchers charted growth patterns, karyotype (Q-banding analysis), expression of typing proteins (fibroblast surface protein and cytokeratin 20) and morphometric parameters (diameters and their ratio, perimeter, area and perimeter/area ratio at computerised image analysis)
They were able to successfully culture primary cells in 78% of the collected duodenal biopsies. Cultured cells, expressing the fibroblast surface protein, tested negative for cytokeratine 20 and maintained a normal kariotype. Cells grew slowly with no differences between the celiac and the non-celiac group. Morphometric analysis of celiac fibroblasts showed substantially increased size, with a preserved diameters ratio, and a reduced perimeter/area ratio.
For the first time, researchers have shown the feasibility of culturing primary fibroblast cells from endoscopic duodenal biopsies in celiac and non-celiac subjects.
This ability shows promise for enhancing studies intended to establish the role of fibroblasts as a possible partaker in the pathogenesis of the celiac mucosal damage.
Source: Journal of Translational Medicine 2009, 7:40

Am J Gastroenterol. 2005 Jan;100(1):177-85 Celiac.com 06/30/2005 – In order to determine whether celiac disease mucosal lesions may have a patchy distribution that would require more than one biopsy sample to make an accurate celiac disease diagnosis, Italian researchers closely examined the detailed biopsies taken from 112 consecutively diagnosed children. All of the children in the study had positive anti-endomysium (EMA) or anti-tissue transglutaminase (tTGA) antibodies, and each underwent an upper GI endoscopy in which 4-5 biopsies were taken from Treitz and/or distal duodenum, intermediate duodenum, proximal duodenum, and the duodenal bulb. All biopsies were then classified according to the Marsh criteria. The researchers diagnosed 110 or the 112 patients with celiac disease, and none of the biopsies taken from these children appeared normal. All those diagnosed were positive for HLA-DQ2 or DQ8 genetic markers. The researchers conclude that: “Mucosal atrophy is present in 85% of patients with celiac disease and total villous atrophy is significantly more frequent in distal duodenum or proximal jejunum. Fifty percent of patients have identical villous atrophy throughout the duodenum and no duodenal areas are histologically normal. In genetically susceptible children with positive serology, a diagnosis of celiac disease can reliably be made even if biopsies are not taken from the distal duodenum or jejunum.”

There are different practices amongst GIs on repeat biopsies vs. serology, and on gluten challenges. My sons g/i, for example, took the position that since my sons symptoms stopped on a gluten-free diet, and his previously sky-high EMA and ARA went back to normal, that it was unnecessary to do either a repeat biopsy or a gluten challenge. From the celiac list correspondence, I now see that my GI is rather liberal.**
Vijay Kumar, M.D., Research Associate Professor at the University of Buffalo and President and Director of IMMCO Diagnostics: I think your sons GI is doing the right thing. That is, if the EMA, ARA are normal (

Vijay Kumar, M.D., Research Associate Professor at the University of Buffalo and President and Director of IMMCO Diagnostics: It is important for the serum tests to be negative in patients with celiac disease. These tests provide strong indicators that the gluten free diet followed is effective and is free of gluten. Sometimes drugs or other intakes may be contaminated with gluten that may continue sensitization and the disease process which may be subclinically. We and others believe once the diagnosis of celiac disease is confirmed and the patient is on a gluten free diet, repeat tests once in 3-6 months may be sufficient.
Karoly Horvath, M.D., Ph.D., Associate Professor of Pediatrics; Director, Peds GI & Nutrition Laboratory; University of Maryland at Baltimore: If a patient has histologically (endoscopy) and serologically (antibody tests) proved celiac disease, and his/her symptoms disappeared on a gluten-free diet, a repeat biopsy is not necessary. The serological tests are useful tools for estimating the effectiveness of the diet after 3-6 months on a gluten-free diet. The disappearance of antibodies from the blood takes months, if there was not any accidental gluten challenge (dietary mistake).

AU- Fallstrom SP; Kristiansson B; Ryd W JN- Acta Pathol Microbiol Scand [A]; 89 (6) p431-8 PY- Nov 1981 AB- Eighty-one children aged 4-18 months with unsatisfactory weight gain were investigated for organic diseases; the investigation included small-intestinal biopsy. Sixteen had total villous atrophy, in most cases due to gluten intolerance. Transient disease, e.g. cows milk protein intolerance, was probable in 7 children with subtotal atrophy. In 18 children the only abnormal finding was an increased number of inflammatory cells in the mucosa, a finding which was probably of no clinical significance. Planimetric measurement showed good agreement between the mucosal surface/volume ratio and an ordinary histological grouping of the mucosa. A significant correlation was found between the rate of weight gain during the period preceding investigation and mucosal surface/volume ratio.